Primary insomnia (PI) is a prevalent and costly health problem among the middle-aged and elderly. Several paradoxes exist regarding pharmacological treatment of PI: Although it is a chronic disorder, hypnotic drugs are approved only for short-term treatment; patients take hypnotics for long period of time, but efficacy has been proven only acutely; hypnotics can cause important adverse effects, but the risks of untreated insomnia have not been carefully controlled; and, although theoretical and clinical evidence suggest that antidepressant drugs have a role in treating PI, no studies have examined their efficacy or adverse effects during maintenance treatment. The NIH does not currently fund any studies on the rational pharmacotherapy of PI. This K24 award addresses these important problems by supporting an established sleep investigator in career development patient- oriented research, and mentoring activities. Career development and training activities will focus on three goals: 1) To develop further skills in the design and implementation of acute and maintenance pharmacotherapy studies for primary insomnia; 2) To develop advanced skills regarding the clinical pharmacology of benzodiazepine receptor agonists (Bz) and antidepressant medications (AD); and 3) To develop further skills in the assessment of clinical outcomes during pharmacotherapy studies for primary insomnia. These goals will be accomplished by meetings with external and departmental consultants, formal coursework, and use of ongoing R01 and center resources within the department as a "learning laboratory." Patient-oriented research activities will focus on design and implementation of a treatment trial comparing a Bz (zolpidem) and an AD (paroxetine) versus placebo for the acute and maintenance treatment of PI. Outcome measures will include global clinical status, subjective and polysomnographic sleep, psychological symptoms, functional status, and performance. Adverse effects, rebound, withdrawal, and recurrence will also be systematically assessed. During the period of award, the Principal Investigator will meet with consultants to finalize study design and selection of outcome measures. He will also collect addition pilot data to support an R01 application for the clinical trial. The goal of mentoring activities is to recruit at least one new trainee per year from the ranks of medical students, residents, or post-doctoral fellows. Success in mentoring will be judged by trainees' productivity in peer-reviewed publications and competition for departmental and external research funds. The Principal Investigator will mentor trainees in analyses of existing data, design and implementation of the clinical trial, described above, and new studies designed by the trainees themselves.